Day and Night Closed-loop in Young People With Type 1 Diabetes (DAN05)
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|ClinicalTrials.gov Identifier: NCT02925299|
Recruitment Status : Completed
First Posted : October 5, 2016
Last Update Posted : February 2, 2021
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The main study objective is to determine whether 24/7 automated closed-loop glucose control combined with low glucose feature will improve glucose control as measured by HbA1c.
This is an open-label, multi-centre, multi-national, single-period, randomised, parallel group design study, involving a 6 month period of home study during which day and night glucose levels will be controlled either by a closed-loop system combined with low glucose feature (intervention group) or by insulin pump therapy alone (control group).
It is expected that a total of up to 150 subjects (aiming for 130 randomised subjects) with type 1 diabetes will be recruited through paediatric outpatient diabetes clinics of the investigation centres. Participants will all be on subcutaneous insulin pump therapy.
Subjects in the intervention group will have proven competencies both in the use of the study insulin pump and the study continuous glucose monitoring (CGM) device, and will receive appropriate training in the safe use of closed-loop insulin delivery system and low glucose feature. All subjects will have regular contact with the study team during the home study phase including 24/7 telephone support. The primary outcome is between group differences in HbA1c levels at 6 months post study arm initiation. Secondary outcomes are the time spent in the glucose target (3.9 to 10.0mmol/l; 70 to 180mg/dl), time spent with glucose levels above and below target, as recorded by CGM, and other CGM-based metrics. Safety evaluation comprises assessment of the frequency of severe hypoglycaemic episodes and diabetic ketoacidosis (DKA).
|Condition or disease||Intervention/treatment||Phase|
|Diabetes Mellitus Diabetes Mellitus, Type 1 Glucose Metabolism Disorders Endocrine System Diseases Autoimmune Diseases||Device: FlorenceM (US) and FlorenceX (UK) Device: Insulin pump therapy||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||131 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open-label, Multi-centre, Randomized, Single-period, Parallel Study to Assess the Efficacy, Safety and Utility of 6 Month Day-and-night Automated Closed-loop Insulin Delivery Under Free Living Conditions Compared to Insulin Pump Therapy in Children and Adolescents With Type 1 Diabetes|
|Actual Study Start Date :||May 12, 2017|
|Actual Primary Completion Date :||August 27, 2020|
|Actual Study Completion Date :||August 27, 2020|
Experimental: 24/7 closed loop insulin delivery
The study system includes (1) a CGM that measures glucose levels, (2) a computer program on a smartphone that determines how much insulin is needed, and (3) an insulin pump that delivers the insulin. The name of this closed-loop system used in the US is FlorenceM (Medtronic 640G pump and Guardian3 sensor). The name of this closed-loop system in the UK is FlorenceX (DANA pump and Dexcom sensor). Half of the individuals taking part in the study will use the closed-loop study system for 6 months.
Device: FlorenceM (US) and FlorenceX (UK)
The automated closed loop system (FlorenceM in US) will consist of:
Next generation sensor augmented Medtronic insulin pump 640G (Medtronic Minimed, CA, USA) incorporating the Medtronic Guardian3 CGM and glucose suspend feature.
The automated closed loop system (FlorenceX in UK) will consist of:
The DANA Diabecare R insulin pump (Sooil Development, Korea) incorporating the Dexcom G6 CGM.
An Android smartphone containing the Cambridge model predictive algorithm and communicating wirelessly with the insulin pump using a proprietary translator device.
Active Comparator: Insulin pump therapy
Half of the Subjects will continue using their own insulin pump for 6 months.
Device: Insulin pump therapy
Subjects will continue using their own insulin pump for 6 months.
- The primary outcome is the centralised measurement of glycated haemoglobin (HbA1c) at 6 months. [ Time Frame: HbA1c will be taken at baseline, 3 and 6 months ]The objective is to assess efficacy of day and night automated closed-loop glucose control combined with low glucose feature in improving HbA1c, as compared with insulin pump therapy alone.
- Time spent in the target glucose range (3.9 to 10mmol/l) (70 to 180mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time spent below target glucose (3.9mmol/l)(70mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time spent above target glucose (10.0 mmol/l) (180 mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Mean and standard deviation or percentiles sensor glucose [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Coefficient of variation of glucose levels [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time with glucose levels < 3.5 mmol/l (63 mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time with glucose levels <3.0 mmol/l (54 mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Time with glucose levels in significant hyperglycaemia (glucose levels > 16.7 mmol/l) (300mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- Changes in total basal and bolus insulin dose [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on CRF and insulin pump data.
- AUC of glucose below 3.5mmol/l (63mg/dl) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- AUC glucose above 10.0mmol/L (180mg/dL) [ Time Frame: 6 months ]Secondary endpoints regarding glucose levels will be based on sensor glucose data.
- HbA1c <7.0%, HbA1c <7.5%, Relative reduction ≥10% from baseline. o Absolute reduction ≥0.5% from baseline o Absolute reduction ≥1% from baseline o Absolute reduction ≥1% from baseline or HbA1c <7.0% [ Time Frame: 6 months ]Binary metrics for HbA1c
- Safety Evaluation [ Time Frame: 6 months ]Frequency of severe hypoglycaemic episodes as defined by American Diabetes Association (adolescents), and International Society for Pediatric and Adolescent Diabetes (children), frequency of diabetic ketoacidosis (DKA), frequency of severe hyperglycaemia (>16.7 mmol/l)(>300mg/dl) with significant ketosis (plasma ketones >0.6mmol/l) and nature and severity of other adverse events
- Utility evaluation [ Time Frame: 6 months ]Assessment of the frequency and duration of use of the closed-loop system
- Human Factors Assessment [ Time Frame: 6 months ]Cognitive, emotional, and behavioural characteristics of participating subjects and family members and their response to the closed-loop system and clinical trial will be assessed gathering both quantitative (validated surveys) and qualitative data (focus groups)
- Health Economic Evaluation [ Time Frame: 6 months ]Cost utility analysis on the benefits of closed loop insulin delivery to inform reimbursement decision-making
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||6 Years to 18 Years (Child, Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- Age ≥6 and <19 years
- Type 1 diabetes as defined by WHO (51) for at least 1 year [WHO definition: 'The aetiological type named type 1 encompasses the majority of cases with are primarily due to beta-cell destruction, and are prone to ketoacidosis. Type 1 includes those cases attributable to an autoimmune process, as well as those with beta-cell destruction for which neither an aetiology nor a pathogenesis is known (idiopathic). It does not include those forms of beta-cell destruction or failure to which specific causes can be assigned (e.g. cystic fibrosis, mitochondrial defects, etc.).']
- Use of an insulin pump for at least 3 months, with good knowledge of insulin self-adjustment by subject or caregiver as judged by the investigator
- Using U-100 rapid acting insulin analogues insulin Aspart or Lispro only
- Willing to perform regular finger-prick blood glucose monitoring, with at least 4 blood glucose measurements per day day
- Screening HbA1c ≥ 7.0% (53 mmol/mol) and ≤10 % (86mmol/mol) based on analysis from local laboratory
- Literate in English
- Willing to wear glucose sensor
- Willing to wear closed-loop system at home
- Willing to follow study specific instructions
- Willing to upload pump and CGM data at regular intervals
- Access to WiFi.
- Lives with someone who is trained to administer intramuscular glucagon and is able to seek emergency assistance
- Living alone
- Current use of any closed-loop system
- Any other physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the study results as judged by the investigator
- Untreated coeliac disease, adrenal insufficiency, or untreated thyroid disease
- Current treatment with drugs known to interfere with glucose metabolism, e.g. systemic corticosteroids, non-selective beta-blockers and MAO inhibitors etc.
- Known or suspected allergy to insulin
- Clinically significant nephropathy (eGFR < 45ml/min) or on dialysis, neuropathy or active retinopathy (defined as presence of maculopathy or proliferative changes) as judged by the investigator
- Recurrent incidents of severe hypoglycaemia (>1 episode) during the previous 6 months (adolescents: severe hypoglycaemia is defined as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions including episodes of hypoglycaemia severe enough to cause unconsciousness, seizures or attendance at hospital; children: severe hypoglycaemia is defined as an event associated with a seizure or loss of consciousness)
- Recurrent incidents of diabetic ketoacidosis (>1 episode) during previous 6 months
- Unwilling to avoid regular use of acetaminophen
- Lack of reliable telephone facility for contact
- Total daily insulin dose ≥ 2 IU/kg/day
- Total daily insulin dose < 15 IU/day
- Pregnancy, planned pregnancy, or breast feeding
- Severe visual impairment
- Severe hearing impairment
- Seizure disorder
- Medically documented allergy towards the adhesive (glue) of plasters or unable to tolerate tape adhesive in the area of sensor placement
- Serious skin diseases (e.g. psoriasis vulgaris, bacterial skin diseases) located at places of the body, which potentially are possible to be used for localisation of the glucose sensor)
- Illicit drugs abuse
- Subject is currently abusing prescription drugs
- Alcohol abuse
- Use of pramlintide (Symlin), or other non-insulin glucose lowering agents including sulphonylureas, biguanides, DPP4-Inhibitors, , GLP-1 analogues, SGLT-1/ 2 inhibitors at time of screening
- Shift work with working hours between 10pm and 8am
- Sickle cell disease, haemoglobinopathy, or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
- Eating disorder such as anorexia or bulimia
- Employed by Medtronic Diabetes or with immediate family members employed by Medtronic Diabetes
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02925299
|United States, California|
|Palo Alto, California, United States, 95032|
|United States, Colorado|
|University of Colorado Denver School of Medicine Barbara Davis Center|
|Aurora, Colorado, United States, 80045|
|United States, Connecticut|
|Hartford, Connecticut, United States, 06520|
|United States, Florida|
|Nemours Children's Health System|
|Jacksonville, Florida, United States, 32207|
|United States, Indiana|
|Indianapolis, Indiana, United States, 43202|
|University of Cambridge|
|Cambridge, Cambridgeshire County, United Kingdom, CB2 0QQ|
|Nottingham Children's Hospital|
|Nottingham, England, United Kingdom, NG5 1PB|
|Southampton Children's Hospital|
|Southampton, England, United Kingdom, SO16 6YD|
|The Leeds Teaching Hospitals NHS Trust|
|Leeds, West Yorkshire, United Kingdom, LS9 7TF|
|Alder Hey Children's NHS Foundation Trust|
|Liverpool, United Kingdom|
|Oxford Children's Hospital|
|Oxford, United Kingdom|
|Study Chair:||Roman Hovorka, PhD||University of Cambridge|
|Principal Investigator:||Ajay Thankamony, MD||University of Cambridge|
|Principal Investigator:||Fiona Campbell, MD||The Leeds Teaching Hospitals NHS Trust|
|Principal Investigator:||Bruce Buckingham, MD||Stanford University|
|Principal Investigator:||Stuart Weinzimer, MD||Yale University|
|Principal Investigator:||Linda DiMeglio, MD||Indiana University|
|Principal Investigator:||Paul Wadwa, MD||University of Colorado, Denver|
|Principal Investigator:||Korey Hood, PhD||Stanford University|
|Principal Investigator:||Dana Goldman, PhD||University of Southern California|
|Principal Investigator:||Nikki C Davis, MD||Southampton Children's Hospital|
|Principal Investigator:||Louise Denvir, MD||Nottingham Children's Hospital|
|Principal Investigator:||Nelly Mauras, MD||Nemours Children's Health System|
|Principal Investigator:||Rachel Besser, MD||Oxford Children's Hospital|
|Principal Investigator:||Atrayee Ghatak, MD||Alder Hey Children's NHS Foundation Trust|
|Responsible Party:||Jaeb Center for Health Research|
|Other Study ID Numbers:||
1UC4DK108520-01 ( U.S. NIH Grant/Contract )
|First Posted:||October 5, 2016 Key Record Dates|
|Last Update Posted:||February 2, 2021|
|Last Verified:||February 2021|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||No|
|Studies a U.S. FDA-regulated Device Product:||Yes|
|Device Product Not Approved or Cleared by U.S. FDA:||Yes|
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Endocrine System Diseases
Immune System Diseases
Physiological Effects of Drugs